Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

The competitive landscape of INVs : An explorative study on competition with well-established MNCs

The purpose of this master’s thesis is to gain a richer understanding of the competitive landscape of INVs and in particular how they compete with well-established MNCs. The existing literature depicts the existence of an untapped potential for extending and enriching the field of international entrepreneurship research heretofore. This exploratory study with its abductive approach applies twelve personal interviews of qualitative nature as the method to collect the data. The ten companies from the multiple-case study are from the biotechnology and pharmaceutical industries. The findings show that although MNCs have a potential to be threats due to their extensive resources, INVs perceive them more as opportunities. Moreover, the study discovers key elements of competition (especially against MNCs), the main common challenges for INVs accordingly, and capabilities that relate to and help accomplish these challenges. These findings do not only have the potential to act as a starting point for further research, but they also contribute to the managerial world by acting as a possible competition guideline for INVs

Lyapunov-type inequalities for nonlinear systems involving the (p1,p2,...,pn)-Laplacian

We prove some generalized Lyapunov-type inequalities for n-dimensional Dirichlet nonlinear systems. We extend the results obtained by Cakmak and Tiryaki [6] for a parameter $1<p_k<2$. As an application, we obtain lower bounds for the eigenvalues of the corresponding system

Oscillation of third-order nonlinear delay difference equations

Third-order nonlinear difference equations of the form Delta(c(n)Delta(d(n)Delta x(n))) p(n)Delta x(n+1) + q(n)f (x(n-sigma)) = n >= n(0) are considered. Here, {c(n)}, {d(n)}, {p(n)} and {q(n)} are sequences of positive real numbers for n(0) is an element of N, f is a continuous function such that f(u)/u >= K > 0 for u not equal 0. By means of a Riccati transformation technique we obtain some new oscillation criteria. Examples are given to illustrate the importance of the results

Factors affecting the accuracy of ultrasonographical fetal weight estimation in twin pregnancies

Objective. To determine the factors affecting the accuracy of ultrasonographic weight estimation in twins

Effect of Nimodipine on Histological Alterations in Basilar Artery Following the Bilateral Common Carotid Artery Ligation (Preliminary Study)

Background: The blood supply to tissues is reduced as a result of arterial occlusions. Angiogenesis, collateral circulation and reverse flow mechanisms go into operation to restore a continued adequate supply of blood. Ca++ channels undertake the major part of this function. As a result of the increasing tension on the arterial walls, vascular autonomy is affected, and ischemia and even necrosis are observed. Method: Adult 100 male hybrid rabbits were used in this study. The bilateral carotid arteries were ligated at the carotid bifurcation. The rabbits were divided into 2 main groups: treatment and control, and then both groups were further divided into 5 subgroups consisting of 10 rabbits each. The rabbits were sacrificed between the first day and the end of 8 weeks for histopathological examination of the basilar artery in two groups. Results: In control groups, after 24 hours of the occlusion partial swelling and minor endothelial damage were observed in histopathological sections of the basilar artery. Luminal flattening started to decrease, and expanding of the diameter continued. The increase in the diameters of the basilar artery was higher in animals treated by nimodipine, and that difference was statistically significant (P=0,000). Conclusion: This study revealed that the intimal and medial alterations arising from the increased blood flow rate in the basilar artery might be lessened and even partially prevented by the use of nimodipine

On the Lyapunov-type inequalities of a three-point boundary value problem for third order linear differential equations

In this paper, by using Green's function for second order differential equations with Dirichlet boundary condition, we establish new Lyapunov-type inequalities for third order linear differential equation which improve all existing results in the literature. As an application, we obtain sharp lower bound for the eigenvalues of corresponding equations and for the distance between the end points in the three consecutive zeros of the solution of the equations. (C) 2015 Elsevier Ltd. All rights reserved